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Several approaches have been proposed recently to provide a quantitative description of the dynamics of populations of proliferating and dying lymphocytes, and to analyze experimental data.
Recent advances in quantitative experimental techniques, in particular intracellular labeling and multi-channel flow cytometry, allow one to measure the population structure of proliferating and dying lymphocytes for several generations with high precision.
As a result, Smith-Martin type models provide a quantitatively better description of the dynamics of the populations of proliferating and dying lymphocytes, and of their generation structure, especially when the rates of cell proliferation are high [18], [20], [24], [32].
It is also crucial to have a theory that incorporates the distribution of inter-division and death times and the generation structure of the dividing and dying lymphocytes, as well as the effects of variation and noise in the dynamics of lymphocyte populations [15], [18] [24].
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Before dying, T lymphocytes experience a phase of functional impairment where cytokine secretion is prohibited.
Proliferating microglia phagocytose pathogens, dying neuronal cells, lymphocytes, and other debris [ 3] and release a wide range of soluble factors, including cytokines, chemokines, and oxygen radicals, to maintain homeostasis in the microenvironment and to support injured neurons in the brain [ 3- 5].
IFN-α actually increases the differentiation of monocytes into dendritic cells that present antigens from dying cells to CD4+ lymphocytes, resulting in their proliferation.
Their sources are probably inflammatory cells; for example, dying human macrophages and lymphocytes produce citrullinated vimentin, which, if released into the extracellular matrix of RA synovium, can specifically react with sera of RA patients.
Most often the invading lymphocytes die by entosis or emperitosis.
In this process, the self-reactive lymphocytes die by apoptosis, while a small percentage of positively selected cells move to the medulla of the thymus where their differentiation proceeds [ 6– 8].
This may, in turn, improve the presentation of tumor antigens from the dying tumor cells to T lymphocytes and thus support antitumor immunity.
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